Phthalate exposure as a hidden risk factor for uterine leiomyoma in adult women: Accumulated evidence from observational studies.

Background: There is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive.

Methods: A meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate.

Results: A total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18-2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00-1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01-1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma.

Conclusion: Our results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.